In the field of medicine, there has been an increasing need to develop implant materials for correction of biological defects. Particularly in the field of orthopedic medicine, there has been the need to replace or correct bone, ligament and tendon defects or injuries. As a result, there have emerged a number of synthetic implant materials, including, but not limited to, metallic implant materials and devices, devices composed in whole or in part from polymeric substances, as well as allograft, autograft, and xenograft implants. It is generally recognized that for implant materials to be acceptable, they must be pathogen free, and must be biologically acceptable. Generally, it is preferable if the implant materials are remodeled over time such that autogenous tissue replaces the implant materials. This goal is best achieved by utilizing autograft tissue from a first site for implantation into a second site.
Joint health is crucial for human mobility and the quality of life. Tendons and ligaments perform to translate and restrain motion respectively about a joint, making them important structures for proper joint functions. Taking the Anterior Cruciate Ligament (ACL) for example, it plays an important role in the normal functioning of the knee joint. However, ACL damage is prevalent as it affects 1 in 3000 Americans each year. When left untreated, the ligament degenerates with the onset of serious diseases such as osteoarthritis. Fortunately, ACL injuries can be addressed with tendon autografts. This treatment is hampered by the inferior integration between the tendon graft and the host bone. This integration site is known as the enthesis and its dysfunction has led to 3000-10000 revision surgeries annually in the United States alone.
To resolve this complication, a physiological understanding of the enthesis is essential. The native ACL anchorage site comprises of a gradient of fibrocartilaginous and calcified tissues that are constituted by a specific arrangement of cellular and Extra Cellular Matrix (ECM) components, which allow for the effective transmission of longitudinal and shear forces from the flexible ligament to the rigid bone. This complex anatomy is not recapitulated during conventional tendon transplantation and it constitutes the weakest region during the healing process. The native enthesis is usually replaced by a soft fibrous tissue, which does not provide adequate bony anchorage. Animal studies have demonstrated tendon pullout failure even after 12 weeks of ACL reconstruction. Spalazzi et al. stressed the need for optimal fibrovascular repair at the tendon bone insertion site to enhance the pull out strength of the graft (Spalazzi J P, Dagher E, Doty S B, Guo X E, Rodeo S A, Lu H H. In vivo evaluation of a tri-phasic composite scaffold for anterior cruciate ligament-to-bone integration. Conf Proc IEEE Eng Med Biol Soc 2006; 1:525-528.). In order to achieve this objective, various fixative methods with a prolonged resting time have been recommended. However, the resultant outcomes are still unsatisfactory.
Current techniques in promoting tendon osteointegration would include the use of specialized grafts and mechanical fixation. Yet, delayed healing and poor integration remained outstanding. Schiavone et al. experimented with a bone-patellar tendon-bone autograft in a rabbit model (Schiavone Panni A, Fabbriciani C, Delcogliano A, Franzese S. Bone-ligament interaction in patellar tendon reconstruction of the ACL. Knee Surg Sports Traumatol Arthrosc 1993; 1(1):4-8.). In their study, native osseous tissue was attached to both ends of the harvested patellar tendon as compared to none for conventional transplants. Interestingly, osseous integration was much longer than that anticipated for regular bone healing. It was reasoned that the healing process with the bone-patellar tendon-bone graft was more complicated than normal bone to bone fusion. To accelerate graft anchorage, mechanical fixation was employed. An example was the use of staples that secured the tendon graft outside the bone tunnel. However, a clinical study conducted by Song et al. (Song E K, Rowe S M, Chung J Y, Moon E S, Lee K B. Failure of osteointegration of hamstring tendon autograft after anterior cruciate ligament reconstruction. Arthroscopy 2004; 20(4):424-428.) indicated poor bonding even after 1.5 years of ACL reconstruction. This was attributed to the insufficient contact between the bone substratum and the tendon graft. Other mechanical means would include spiked washers, transfixation devices, sutures and tape fixation to buttons. Unfortunately, the outcomes were compromised by micromotion between the graft tissue and the surrounding bone. A gross indicator of transplant failure is bone tunnel expansion resulting from the osseous resorption at the insertion site, which occurs as early as 3 months after ACL reconstruction. Other complications would include ganglions, osseous edema, inflammations and sclerosis. These adverse effects were commonplace with commercially available mechanical implants that only provide temporary anchorage without enhancing biological fusion. Consequently, the functionality of the transplanted ACL is compromised thus resulting in the need for revision procedures.
Recently, a variety of materials and solutions have been proposed for improving the healing process of the bone-graft interface, including autologous bone tissue, cells, artificial proteins and calcium salts. One of the emerging materials are the calcium phosphates (CaP), which are known for their biocompatibility and are widely available commercially. Although CaPs have been shown to advance the healing of bone tunnel tissue in animal studies, it does not consist of a biological phase nor allows feasible incorporation of cells to the system. As such, the method is limited to being an osteoconductive approach, instead of an osteoinductive one. In another words, osteointegration will only depend on the native osteoblasts from the bone tunnel and not from within the interfacial CaP material.
Another method is the use of periosteum, harvested from the proximal tibia by a routine incision used to harvest hamstring tendons, to augment the graft-bone interface. This autologous material has the potential of improving tendon-bone healing, and may help to seal the intraarticular tunnel opening quickly after surgery and avoid reflux of synovial fluid into the tunnel. Bone tunnel enlargement could be reduced. Nevertheless, the periosteum will have to be autologous, limiting its application as an off-the-shelf product.
At present, the success of tendon or ligament transplantation techniques is severely curtailed by the poor anchorage of the grafts due to insufficient biological integration. Conventional fixative techniques emphasized mechanical bonding. However, there is need in the art for alternative strategies to improve ligament/tendon reconstruction.